The synthesis of metoprolol monitored using Raman spectroscopy and chemometrics

The synthesis of Metoprolol base was studied using Raman spectroscopy with a 785-nm laser, optical fibres, a holographic transmission grating, confoca l optics and a charge-coupled device (CCD) detector. The reaction mixture w as heated according to a temperature gradient and spectra of the reaction m ixture were obtained by focusing the laser beam through ordinary reaction f lasks. Because of overlapping bands, multivariate techniques such as princi pal components analysis (PCA) and partial least-squares projections to late nt structures (PLS) were used in the evaluation of the obtained spectra. Th e use of PCA or PLS against, time does not require any calibration samples and a quantitative calibration is not necessary in order to monitor the rea ction. A method for reaction endpoint determination, based on euclidean dis tances in the score space, is presented. The use of multivariate batch cont rol charts have been demonstrated and a number of problems and solutions re garding the sample presentation have been discussed. The effect of spectral pretreatment on the multivariate results is shown and discussed. The monit oring results show that the time to produce Metoprolol base could be reduce d. (C) 2000 Elsevier Science B.V. All rights reserved.